Consumption of tea is associated with numerous cancer preventative activities and epidemiological evidence suggests a specific role in reducing cancers of the gastrointestinal (Gl) tract. With evidence supporting a potential chemopreventative role for tea, studies have focused on tea polyphenols, and more specifically tea catechins, as potential cancer preventative agents. However, stability of tea catechins to digestive conditions is known to be poor, suggesting that catechin digestive products may actually be responsible, in part, for the chemopreventative activity of this beverage. Currently, very little is known regarding the full digestive fate of tea catechins, and/or the effects of digestion on tea cancer preventative activities. Due to this gap in knowledge, it is unclear whether native catechins or products of catechin digestive breakdown are most critical to observed cancer preventative activities. Our long-term goal is to determine physiological relevance of dietary phytochemical constituents. Our overall objective is to determine the effects of human digestion on tea catechin cancer preventative activity and characterize major digestive end-products of catechin origin that may differ from native catechins currently believed to be physiologically active agents. Specific Aims for this study are: (1) To characterize tea catechin digestive behavior and formation of digestive end-products. We will use an in vitro digestive model to determine effects of gastric and small intestinal conditions on tea catechin profile. By use of HPLC-MS and MS/MS techniques we will characterize major tea polyphenol forms present in the intestinal lumen; (2) To establish the effect of digestive catechin modification on cancer preventative activity. Differences in cancer preventative activity of native (undigested) and digested catechins will be compared by in vitro screening assays focused on gastric and colon cancer cell proliferation, intracellular oxidative stress (DCF and NFkB activity assays), and regulation of Phase II enzyme activity (i.e. quinone reductase). Relevance: Our studies will determine the influence of human digestion on the cancer preventative activities of tea catechins. Discovery of tea compounds which hold ultimate biological significance will enable future experimental strategies for specific tea catechin forms that positively affect cancer risk and outcomes. [unreadable] [unreadable] [unreadable]